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Administrative data

Description of key information

Oral (OECD 401): LD50 values > 5000 mg/kg bw
Inhalation (OECD 436): LC50 > 5.7 mg/L air
Dermal: no data available

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 - 19 Mar 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study with acceptable restrictions. No gross necropsy performed, no details on animal husbandry, observation period 7 days in the absence of mortality/signs of toxicity, few details on study protocol, analytical purity not given.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
no gross necropsy performed, no details on animal husbandry, few details on study protocol, observation period 7 days in the absence of mortality/signs of toxicity
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
mouse
Strain:
other: NMRI EOPS
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 19-20 g (range)
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5.8 mL/kg bw, (dose calculated assuming test substance density of 0.8550 g/mL)
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days (in the absence of mortality and signs of toxicity)
- Frequency of observations and weighing: mortality was recorded daily; the animals were observed daily for the presence of clinical signs; body weights were determined on Day 0 and 6
- Necropsy of survivors performed: no
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study period.
Clinical signs:
other: No clinical signs of toxicity were observed up to the end of the 7-day observation period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
03 Jun - 17 Jun 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Version / remarks:
adopted in 2009
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 9 weeks old
- Weight at study initiation: max. ± 20% of the sex mean
- Housing: Before exposure-Group housing of maximally 5 animals per sex per cage in labeled Makrolon cages (type IV; height 18cm.) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, UK). After exposure - Group housing as described above, maximally 3 animals per sex per cage.
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäteb GmbH, Soest, Germany), ad libitum except during exposure to the test substance.
- Water: tap-water, ad libitum except during exposure to the test substance.
- Acclimation period: 5 days before the start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To:
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: The design of the exposure chamber is based on the flow past nose-pnly inhalation chamber (Am.Ind.Hyg Assoc.J. 44(12): 923-928, 1983). The chamber consists of animal sections with eight animal ports each. Each animal port has its own atmosphere inlet and exhaust outlet.

- Method of holding animals in test chamber: Animals are placed in restraining tubes, which is then connected to the exposure chamber.

- Source and rate of air: The theoretical air flow was at least 1L/min.

- System of generating aerosols: An aerosol was generated by nebulization of the test substance by means of a nebulizer (type 950,
Hospitak Inc., Lindenhurst, NY, USA). The primary aerosol was diluted with pressurized air before it entered the exposure chamber. The mean total airflow was 16 L/min. From the exposure chamber the test atmosphere was passed through a filter before it was released to the exhaust of the fume hood.

- Method of conditioning air: The direction of the flow of the test atmosphere guarantees a freshly generated atmosphere for each individual animal.

- Temperature, humidity, pressure in air chamber: The temperature of the atmosphere was between 20.0 and 20.7 °C and relative humidity was between 28 and 30%. These conditions were considered appropriate for the relatively short 4 hours exposure duration.


TEST ATMOSPHERE
- Brief description of analytical method used: Samples were drawn through a glass fiber filter (type APFC04700, Millipore, Billerica, MA, USA). The collected amount of test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).
- Samples taken from breathing zone: yes


VEHICLE
- The test substance was used as delivered by the sponsor

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD was 2.5 µm (GSD 2.4) and 2.6 µm (GSD 2.3).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Target concentrations were based on the cut off concentration values specified in the UN and EC classification guidelines.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetrically
Duration of exposure:
4 h
Concentrations:
The mean actual concentration was 5.7 ± 0.4 mg/L. The nominal concentration was 15.4 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 37%. Data obtained from the opacity monitor showed that the aerosol was sufficiently stable.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: twice daily
Clinical signs: twice on the day of dosing (1 and 3 hours after exposure); daily thereafter until day 15
Body weight: recorded on day1 (pre-exposure), 2, 4, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
All animals were sacrificed at the end of the observation period by an intraperitoneal injection with Euthasol® (AST Farma BV, Oudewater, The Netherlands).
Statistics:
No statistical analysis was performed (the method used was not intended to calculate a LC50 value).
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.7 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortalities occured. Apart from hunched position observed in all on day2 after exposure, no further signs of adverse toxicity were observed until the end of the 14 day observation period.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 15.4 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortalities occured during the 14-day observation period.
Clinical signs:
other: Hunched posture was shown by all animals on Day 2 after exposure. No clinical signs were noted during exposure.
Body weight:
Body weight gain in males and females were within the range expected for rats of this strain and age used in this type of study.

Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional groups, common precursors/breakdown products and similarities in physicochemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are no data available on the acute inhalation toxicity of isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2). In order to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview of acute toxicity

CAS

Chemical name

Molecular weight

Acute toxicity Oral

Acute toxicity inhalation

Acute toxicity dermal

111937-03-2 (a)

Isononanoic acid, C16-18 alkyl esters

382.66; 410.72

Experimental result:
LD50 >5000 mg/kg bw (mouse)
LD50 >17010 mg/kg bw (rat)

RA: CAS 26399-02-0

Waiving

26399-02-0 (b)

2-ethylhexyl oleate

394.67

Experimental result:
LD50 >5000 mg/kg bw (mouse)

Experimental result:
LC50 >5.7 mg/L air (analytical)

--

(a) Substances subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Acute oral toxicity

CAS 111937-03-2

In a study comparable to OECD 401, 5 female mice were administered 5000 mg/kg bw isononanoic acid, C16-18 alkyl esters (CAS 111937-03-2) (Dufour, 1991). No mortality occurred. No clinical signs were observed and the body weight was not affected during the 7-day observation period. No necropsy examinations were performed at sacrifice. The LD50 is considered to be > 5000 mg/kg bw.

In a study performed by Potokar (1970), 10 male rats/dose were administered 10 mL/kg bw isononanoic acid, C16-18 alkyl esters as a 50% solution of the test substance in olive oil and 19.9 mL/kg bw of the undiluted test substance (equivalent to 8.55 and 17.01 g/kg bw, respectively). No mortality occurred, and no clinical signs were reported during the 7-day observation period. Based on the limited data available, the LD50 is considered to be > 17.01 g/kg bw. 

Acute inhalation toxicity

CAS 26399-02-0

The acute inhalation toxicity of 2-ethylhexyl oleate (CAS 26399-02-0) was assessed in a study performed according to OECD 436 (Van Huygevoort, 2010). 3 rats/sex were exposed to 5.7 ± 0.4 mg/L (actual concentration) of the test substance as an aerosol via nose-only exposure for 4 hours. The nominal concentration was 15.4 mg/L and the MMAD was 2.1-2.5 µm. No mortality occurred. The animals had a hunched posture on Day 2; no further clinical signs were observed during the 14-day study period. The body weight gain was within the range that is normal for this strain and study type. No findings were reported during the macroscopic examination. The LC50 is considered to be > 5 mg/L.

Acute dermal toxicity

This information is not available.

Conclusions for acute toxicity

The available acute oral toxicity data showed that no mortality occurred and the LD50 was > 5000 mg/kg bw. No mortality was observed in the acute inhalation study, leading to an LC50 of > 5 mg/L (Van Huygevoort, 2010). There are no data available on the acute dermal toxicity of isononanoic acid, C16-18 alkyl esters. However, the physicochemical properties of the substance (molecular weight: 382.66-410.72 g/mol, log Pow > 6, water solubility < 0.05 mg/L) are in a range that anticipate a lower dermal absorption rate than via the oral and inhalation route. Since the substance is neither acute toxic by the oral route (LD50 > 5000 mg/kg bw) nor skin or eye irritating and there are no indications for a skin sensitising potential, it is unlikely that acute dermal exposure would lead to toxic effects at dose levels lower than the oral LD50. Therefore, testing for acute toxicity by the dermal route is also deemed scientifically unjustified in accordance with Annex XI, Section 1.2 of Regulation (EC) 1907/2006, based on the weight of evidence from the available physicochemical and toxicological data documented in the technical dossier and the Chemical Safety Report. Hence, further testing on vertebrate animals for this property shall be omitted.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.


Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study with the lowest dose descriptor.

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on substance-specific studies and read-across from structurally similar substances, the available data on the acute oral and inhalation toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

There are no data available on acute dermal toxicity.

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